Heat Shock Factor 4 Regulates the Expression of HSP25 and Alpha B-crystallin by Associating with DEXD/H-box RNA Helicase UAP56

Overview

Journal Cell Stress Chaperones

Publisher Elsevier

Specialty Cell Biology

Date 2017 Nov 23

PMID 29164525

Citations 1

Authors

Xiukun Cui

Wenxiu Han

Jing Li

Riping Feng

Zheng Zhou

Jiuli Han

Mengyuan Li

Shuangfeng Wang

Wanting Zhang

Qin Lei

Jun Zhang

Yutiao Liu

Yanzhong Hu

Affiliations

Soon will be listed here.

Abstract

Heat shock factor 4 controls the transcription of small heat shock proteins (e.g., HSP25, alpha B-cyrstallin, and r-crystallin), that play important roles in modulating lens proteostasis. However, the molecular mechanism underlying HSF4-mediated transcription is still unclear. Using yeast two hybrid, we found that HSF4 interacts with the ATP-dependent DEXD/H-box RNA helicase UAP56, and their interaction in lens epithelial cell line was further confirmed by GST-pull down assay. UAP56 is a vital regulator of pre-mRNA splicing and mature mRNA nuclear export. The immunofluorescence assay showed that HSF4 and UBA56 co-localize with each other in the nucleus of lens epithelial cells. Ectopic UAP56 upregulated HSF4-controlled HSP25 and alpha B-crystallin proteins expression, while knocking down UAP56 by shRNA reversed it. Moreover, UAP56 interacts with and facilitates the nuclear exportation of HSP25 and alpha B-crystallin mRNA without impacting their total mRNA expression level. In lens tissues, both UAP56 and HSF4 are expressed in the same nucleus of lens fiber cells, and their expression levels are simultaneously reduced with fiber cell maturation. Taken together, these data suggested that UAP56 is a novel regulator of HSF4 and might upregulate HSF4's downstream mRNA maturation and nuclear exportation.

Citing Articles

More Than Meets the Eye: Revisiting the Roles of Heat Shock Factor 4 in Health and Diseases.

Syafruddin S, Ling S, Low T, Mohtar M Biomolecules. 2021; 11(4).

PMID: 33807297 PMC: 8066111. DOI: 10.3390/biom11040523.

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